Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000563249 | SCV000673773 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-10 | criteria provided, single submitter | clinical testing | The p.E924K variant (also known as c.2770G>A), located in coding exon 11 of the MET gene, results from a G to A substitution at nucleotide position 2770. The glutamic acid at codon 924 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Mendelics | RCV000709039 | SCV000838265 | uncertain significance | Papillary renal cell carcinoma type 1 | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001358797 | SCV000948479 | uncertain significance | Renal cell carcinoma | 2023-11-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 924 of the MET protein (p.Glu924Lys). This variant is present in population databases (rs778115147, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MET-related conditions. ClinVar contains an entry for this variant (Variation ID: 485757). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MET protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Sema4, |
RCV000563249 | SCV002532137 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-27 | criteria provided, single submitter | curation | |
| Gene |
RCV003128631 | SCV003805562 | uncertain significance | not provided | 2023-02-09 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |